title: Synthetic mimics of antimicrobial peptides from triaryl scaffolds.
abstract: In this report, we describe the synthesis of a new series of small amphiphilic aromatic compounds that mimic the essential properties of cationic antimicrobial peptides using Suzuki-Miyaura coupling. The new design allowed the easy tuning of the conformational restriction, controlled by introduction of intramolecular hydrogen bonds, and the overall hydrophobicity by modifications to the central ring and the side chains. This approach allowed us to better understand the influence of these features on the antimicrobial activity and selectivity. We found that the overall hydrophobicity had a more significant impact on antimicrobial and hemolytic activity than the conformational stiffness. A novel compound was discovered which has MICs of 0.78 μg/mL against S. Aureus and 6.25 μg/mL against E. Coli, similar to the well-known antimicrobial peptide, MSI-78.
authors.affiliation: Department of Polymer Science and Engineering, University of Massachusetts, Amherst, Massachusetts 01003, United States.
authors.forename: Hitesh D
authors.initials: HD
authors.lastname: Thaker
authors.forename: Federica
authors.initials: F
authors.lastname: Sgolastra
authors.forename: Dylan
authors.initials: D
authors.lastname: Clements
authors.forename: Richard W
authors.initials: RW
authors.lastname: Scott
authors.forename: Gregory N
authors.initials: GN
authors.lastname: Tew
mesh_terms: D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D001419:Bacteria / Q000187:drug effects; D015195:Drug Design; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D057786:Peptidomimetics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D023181:Antimicrobial Cationic Peptides; D057786:Peptidomimetics